Aims:Surgical repair infrequently restores the native tendon-bone interface (TBI, also referred to as the enthesis), resulting in excessive scar formation, compromised biomechanics, and frequent re-tears. A simple, biodegradable surgical adjunct that supports tendon-bone healing could augment standard repair strategies. In this study, we evaluated a biomimetic, amino acid-based biodegradable polyurethane adhesive as an intraoperative adjunct to standard suture repair in a rat Achilles tendon-calcaneus model. Methods:A total of 90 female Sprague-Dawley rats (8 weeks old) were randomly assigned to two groups: suture-only and suture + adhesive (n = 45 per group). In the enthesis injury model, after transection and drilling, the polymer adhesive was freshly prepared and applied directly to the tendon-bone interface prior to suture tightening. The contralateral limb served as an intact control. Animals were sacrificed at four-, eight-, and 12-week timepoints, and tissues were evaluated using histological, imaging, micro-CT, and biomechanical analyses. Results:Compared with suture-only repair, the suture + adhesive treatment was associated with more organized fibrocartilage formation, improved collagen I/III organization, greater proteoglycan deposition, and a smaller, more compact repair interface. When normalized by cross-sectional area, the adhesive group exhibited higher ultimate stress (tissue-level mechanical strength), although ultimate stress remained below that of intact controls. Whole-construct mechanical properties were comparable between groups, suggesting that the adhesive served as a biological and structural adjunct that was associated with improved intrinsic tissue quality, rather than increased construct-level strength. Conclusion:These findings suggest that a biodegradable polyurethane adhesive is associated with improved structural organization and intrinsic tissue-level mechanical properties of the repaired tendon-bone interface. Its straightforward intraoperative use and favourable biocompatibility profile support further investigation of its potential as an adjunctive strategy for tendon-bone repair.
Aims:There is currently no validated noninvasive method to determine infection control prior to prosthesis reimplantation during the two-stage revision process for hip periprosthetic joint infections (PJI) after total hip arthroplasty (THA). This prospective study investigates whether metal artifact reduction sequence (MARS) MRI can serve as a diagnostic reference for infection control before second-stage revision surgery by analyzing artifact-reduced MRIs in patients with hip PJI prior to reimplantation. Methods:Patients with hip PJI after THA who entered the two-stage revision process between January 2019 and January 2024 were prospectively and consecutively enrolled. Based on the Musculoskeletal Infection Society (MSIS) criteria, 23 patients achieved infection control after the interval period (prior to reimplantation), and 11 experienced infection recurrence after spacer implantation (prior to repeat debridement). All patients underwent MARS MRI prior to both first-stage surgery and second-stage reimplantation. Data collected included patient demographics (sex, age), ESR, CRP, intraoperative pathology, culture results, and MARS MRIs. Two imaging specialists reviewed the MARS MRIs obtained prior to the first-stage surgery and prior to the second-stage reimplantation, evaluating regression of prior infectious lesions, emergence of new lesions, and overall infection control. Their assessments were then compared with intraoperative pathology and culture-confirmed infection status. Results:MARS MRI revealed significantly more frequent findings of bone oedema, soft-tissue oedema, and joint effusion in patients with recurrent infection compared to those with controlled infection after spacer implantation (p = 0.002). The imaging specialists' evaluations were in complete agreement with the clinical findings confirmed by pathology and cultures. Conclusion:Evaluating the difference in MARS MRIs between the first-stage and second-stage preoperative periods, and focusing on oedema signals in the bone and soft tissues surrounding the prosthesis, provides a useful noninvasive indicator for determining infection control prior to two-stage reimplantation.
Aims There is currently no validated noninvasive method to determine infection control prior to prosthesis reimplantation during the two-stage revision process for hip periprosthetic joint infections (PJI) after total hip arthroplasty (THA). This prospective study investigates whether metal artifact reduction sequence (MARS) MRI can serve as a diagnostic reference for infection control before second-stage revision surgery by analyzing artifact-reduced MRIs in patients with hip PJI prior to reimplantation. Methods Patients with hip PJI after THA who entered the two-stage revision process between January 2019 and January 2024 were prospectively and consecutively enrolled. Based on the Musculoskeletal Infection Society (MSIS) criteria, 23 patients achieved infection control after the interval period (prior to reimplantation), and 11 experienced infection recurrence after spacer implantation (prior to repeat debridement). All patients underwent MARS MRI prior to both first-stage surgery and second-stage reimplantation. Data collected included patient demographics (sex, age), ESR, CRP, intraoperative pathology, culture results, and MARS MRIs. Two imaging specialists reviewed the MARS MRIs obtained prior to the first-stage surgery and prior to the second-stage reimplantation, evaluating regression of prior infectious lesions, emergence of new lesions, and overall infection control. Their assessments were then compared with intraoperative pathology and culture-confirmed infection status. Results MARS MRI revealed significantly more frequent findings of bone oedema, soft-tissue oedema, and joint effusion in patients with recurrent infection compared to those with controlled infection after spacer implantation (p = 0.002). The imaging specialists’ evaluations were in complete agreement with the clinical findings confirmed by pathology and cultures. Conclusion Evaluating the difference in MARS MRIs between the first-stage and second-stage preoperative periods, and focusing on oedema signals in the bone and soft tissues surrounding the prosthesis, provides a useful noninvasive indicator for determining infection control prior to two-stage reimplantation. Cite this article: Bone Joint Res 2026;15(9):1101–1110.
Aims:Accurate registration of anatomy is fundamental to robotic and computer-assisted surgery; however, conventional methods rely on manual data acquisition performed by the surgeon using a tracked probe that is slow and affected by operator variability. Limitations of manual methods have hindered wider adoption of surgical navigation despite its benefits for alignment accuracy, particularly in orthopaedic applications. This study evaluates a laser surface scanning system, LumaScan, against standard intraoperative probe-based registration with a controlled phantom knee model. Methods:Surgeons performed repeated probe-based data acquisition for registration, while LumaScan executed operator-initiated scans mounted to a robotic arm. The accuracy of each modality was assessed using root mean square (RMS) error relative to a CT-derived reference model, alongside evaluations of repeatability and acquisition time. Results:LumaScan achieved a RMS error of 0.07 mm (SD 0.02), compared to probe-based methods, which resulted in a RMS error of 0.34 mm (SD 0.36). Acquisition time was reduced from 112 seconds (SD 75.8) manually to 6.38 seconds (SD 0.03) for LumaScan (p < 0.001), with probe-based timing increasing three times from the fastest to the slowest participant despite a fixed protocol. The errors of the femur and tibia achieved by LumaScan had a > 70% reduction compared to manual surface acquisition, with these results being statistically significant (p < 0.001). The results demonstrate that robotic laser scanning can significantly improve speed, accuracy, and precision over manual methods. Minimizing operator influence and standardizing registration has the potential to reduce error sources that persist in clinical workflows, subsequently accelerating the integration of navigation and robotics into routine orthopaedic procedures. Conclusion:LumaScan enables faster, more accurate, and more precise anatomical registration than manual methods.
Aims:To biomechanically compare the stability of mini-plate and dual-screw fixation following minimally invasive distal metatarsal osteotomy for hallux valgus, with an emphasis on early-stage stability under clinically relevant loading conditions. Methods:Three fixation configurations were evaluated: mini-plate fixation with two (PS2) or three (PS3) locking screws and dual-screw fixation (DS). Finite element analysis (FEA) was performed to quantify displacement and stress distribution under controlled bending and torsional loading, providing insight into internal load transfer mechanisms not accessible experimentally. Fresh-frozen human cadaveric specimens then underwent distal chevron metatarsal osteotomy and fixation according to each configuration (n = 3 per group). Cyclic and static bending tests were performed to simulate early postoperative weightbearing, and displacement responses were recorded. FE predictions were compared with experimental displacement trends. Results:Under bending loads, both FEA and cadaveric testing consistently demonstrated that PS3 exhibited the smallest displacement, followed by PS2, with DS showing the greatest instability. FE analysis further revealed that mini-plate fixation reduced bone stress at the osteotomy site but increased implant stress, whereas DS showed higher bone stress concentration. Under torsional loading, FE results indicated lower displacement but higher bone stress in DS. Cadaveric cyclic tests confirmed the superior stability of PS3, showing the least displacement accumulation over 1,000 cycles (p < 0.05). In static testing, PS3 achieved the highest failure load (~423 N), followed by PS2 (~248 N), while DS showed the lowest (~205 N). Conclusion:Mini-plate fixation, particularly PS3, provides superior resistance to bending-induced micromotion compared with DS, with consistent agreement between FE predictions and experimental findings. FEA further elucidated internal stress distribution, highlighting increased bone stress concentrations in DS. Overall, mini-plate fixation offers a more stable and clinically reliable construct for maintaining correction during early postoperative weightbearing.
Aims This study aimed to investigate the role of AHNAK in patients with osteonecrosis of the femoral head (ONFH) and its association with bone adipogenesis. Non-traumatic ONFH, primarily driven by steroid use and alcohol consumption, results in an imbalance between osteogenesis and adipogenesis. Understanding the function of AHNAK under ischaemic stress may help identify novel therapeutic targets for ONFH. Methods Bone tissues from 19 ONFH patients and 15 control patients were analyzed using proteomics, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF). A steroid-induced ONFH mouse model and an ischaemia-mimicking in vitro model using MC3T3-E1 preosteoblasts were employed to examine AHNAK expression and function. AHNAK knockdown was performed using short hairpin RNA (shRNA) to assess its regulatory effects on adipogenic markers and Smad/PPARγ/C/EBPα signalling. Results AHNAK expression was significantly upregulated in bone tissues of ONFH patients and in femoral heads of steroid-induced ONFH mice. This was accompanied by reduced osteocyte numbers and increased adipogenesis, as indicated by elevated perilipin 1 (PLIN1) expression. In vitro, ischaemic stress induced AHNAK and PLIN1 expression, whereas AHNAK knockdown reversed these effects and suppressed Smad1/5 phosphorylation and PPARγ activation. C/EBPα expression remained unchanged, suggesting a selective role of AHNAK in modulating the Smad/PPARγ axis during adipogenesis. Conclusion AHNAK is a critical mediator of ischaemia-induced adipogenesis in ONFH through activation of the Smad/PPARγ signalling pathway, promoting the differentiation of preosteoblasts into adipocytes. Targeting AHNAK may offer a novel therapeutic strategy to reduce bone loss and marrow fat accumulation in ONFH, particularly in cases associated with steroids or metabolic dysfunction. Further studies are warranted to validate AHNAK as a clinical target. Cite this article: Bone Joint Res 2026;15(8):1042–1054.
Aims Epidural fibrosis is a major cause of failed back surgery syndrome following laminectomy. While previous studies have focused primarily on the early phases of scar formation, fibrotic remodelling remains poorly understood. This study aimed to investigate the interaction between collagen accumulation and fibroblasts during the remodelling phase of epidural fibrosis. Methods In this study, a 3D collagen encapsulation model was used to simulate mechanical stress. Fibrotic and mechanosensitive pathway-related molecules were analyzed to assess fibroblast activation, and specific pharmacological inhibitors were applied to verify the proposed mechanism. Additionally, a mouse laminectomy model was used to evaluate the therapeutic effect of Piezo1 blockade on epidural fibrosis. Results We found that collagen fibres encapsulate fibroblasts during the stage of scar remodelling. In vitro, collagen may activate the transforming growth factor beta-1 (TGF-β1)/Smad3 pathway in fibroblasts, which is mediated by the Piezo1 and hypoxia-inducible factor 1-alpha (HIF-1α) signalling pathways. This process establishes a positive feedback loop between collagen accumulation and fibroblast activation. Furthermore, we demonstrated that Piezo1-mediated activation of HIF-1α occurs through calcium ion influx and stabilization of endothelin-1 (ET-1). More importantly, blocking the activation of Piezo1 attenuated fibrosis progression in a mouse model of laminectomy. Conclusion These results highlight the critical role of the Piezo1/ET-1/HIF-1α pathway in epidural fibrotic remodelling. Targeting Piezo1 may offer a promising therapeutic strategy for alleviating epidural fibrosis and improving outcomes after spinal surgery. Cite this article: Bone Joint Res 2026;15(8):1017–1032.
Aims Infective arthritis is rare, but serious. Timely treatment with appropriate antimicrobial therapy is potentially life- and limb-saving, but our ability to deliver this is limited by current laboratory practices, which confer a delay of several days before antimicrobial sensitivities are available. We propose a novel diagnostic modality, the Scattered Light Integrating Collector (SLIC), which monitors bacterial growth in real time, allowing a diagnosis of infection to be made in minutes, and antimicrobial sensitivities to be delivered in under an hour. Methods We collated data previously collected on SLIC relating to laboratory strains of Staphylococcus aureus 25923 and methicillin-resistant S. aureus (MRSA) 29213 . Liquid cultures of the two organisms, with varying dilutions of target antibiotics, were compared in SLIC against positive (no antibiotic) and negative (no bacteria) controls. Three key measurements were derived: time to positivity (TTP - the timepoint at which significant bacterial growth was confirmed), time to sensitivities (TTS - the timepoint of statistically significant growth inhibition conferred by antibiotics vs the positive control), and IC50 (50% growth suppression relative to control). Results TTP for S. aureus and MRSA was two minutes and 2.2 minutes, respectively. S. aureus was sensitive to gentamicin, with a minimum TTS of one minute, and IC50 achieved in under 19 minutes for all doses. Similarly, S. aureus susceptibility to vancomycin was established, with a minimum TTS of three minutes, and IC50 achieved in under 55 minutes for all but the lowest dose. MRSA was sensitive to rifampicin, with IC50 achieved in 16.5 minutes. Despite all tested antibiotics achieving TTS in under 30 minutes, only rifampicin achieved the criterion IC50 to declare susceptibility. Conclusion SLIC rapidly determines the presence of infection and characterizes antimicrobial susceptibilities in organisms typical for joint infection. Cite this article: Bone Joint Res 2026;15(8):1005–1016.
Aims:Extensor mechanism disruption is a major complication following total knee arthroplasty, with treatment often consisting of extensor mechanism reconstruction utilizing monofilament polypropylene mesh (Marlex mesh, C. R. Bard, Inc). Infection following this procedure is devastating, often resulting in revision surgery and mesh removal, with permanent limb dysfunction. This study evaluated the in vitro ability of vancomycin-loaded polypropylene mesh to inhibit growth of isolates of three Staphylococcus species from patients with periprosthetic joint infection. Methods:The mesh was prepared in two configurations - single-layer and eight-layer - and soaked for ten minutes in either sterile water (control) or vancomycin solution (50 mg/ml), after which the mesh was placed on tryptic soy agar plates inoculated with staphylococci and incubated at 37°C for 18 to 24 hours. Zones of inhibition were measured daily over seven days, with mesh transferred to freshly inoculated plates daily. Testing was performed in triplicate, with experiments repeated three times for each bacterial isolate. A total of 30 clinical isolates were tested (five methicillin-susceptible Staphylococcus epidermidis, five methicillin-resistant S. epidermidis, ten methicillin-resistant Staphylococcus aureus, and ten Staphylococcus lugdunensis). Results:Across all species, the eight-layer vancomycin-loaded mesh produced statistically significantly larger median zones of inhibition than the single-layer mesh. The antibacterial activity of the eight-layer mesh persisted through to day 7, while the single-layer mesh showed reduced activity by days 4 to 5. Conclusion:Compared with single-layer vancomycin-loaded mesh, multilayer vancomycin-loaded mesh, which mimics clinical application, provides enhanced and sustained antibacterial activity in vitro.
Aims Chronic bone and joint infections caused by Staphylococcus epidermidis can be difficult to treat and are prone to recurrence. In this study, established human osteoblast- and osteocyte-like cell line models were used in vitro to investigate the intracellular persistence of S. epidermidis as a potential mechanism for infection persistence. Methods The SaOS2 human osteosarcoma cell line was differentiated into osteoblast-like (SaOS2-OB) and osteocyte-like (SaOS2-OY) stages and infected with four S. epidermidis strains at varying multiplicities of infection. Susceptibilities to lysostaphin, a known bacteriolytic enzyme, and a panel of antibiotics were determined to identify an antimicrobial capable of clearing extracellular bacteria while preserving intracellular bacterial viability. Bacterial survival and number were quantified by colony-forming unit and droplet digital polymerase chain reaction (PCR), while host gene expression was analyzed by real-time PCR. Results Lysostaphin was ineffective against all four S. epidermidis strains, while 10 × minimal bactericidal concentration levofloxacin consistently eliminated extracellular but not intracellular bacteria. Intracellular S. epidermidis at multiplicities of infection of 1,000 persisted in SaOS2-OY for 14 days at 10 × minimal bactericidal concentration levofloxacin, while it was cleared within five days in SaOS2-OB cells. Droplet digital PCR genome copy analysis identified a higher number of bacteria than conventional culture, indicating more accurate counting and a transition of the intracellular bacteria to a non-culturable state. Proinflammatory and bone remodelling responses by both bone cell types were evident upon infection, with increased messenger RNA levels of CCL5 , CXCL6 , CXCL10 , SOST , receptor activator of nuclear factor kappa-B ligand ( RANKL ), and matrix metalloproteinase 13 ( MMP13 ). Conclusion We report the first model of intracellular S. epidermidis persistence in osteocyte-like cells, which provides a robust platform for mechanistic studies of chronic bone and joint infections and the preclinical screening of novel therapeutics targeting intracellular bacteria. Cite this article: Bone Joint Res 2026;15(8):987–997.
Aims:Femoral shaft fractures are commonly associated with high-energy trauma, and affect individuals of all ages. Kidney dysfunction frequently complicates fracture healing, and trauma-related acute kidney injury (TRAKI) elevates the risk of adverse outcomes. The mechanisms of post-fracture kidney injury, particularly the involvement of sympathetic activation, remain poorly understood. We aimed to define the impact of femoral fracture on the kidney and investigate mechanistically the potential contribution of sympathetic activation. Methods:A total of 46 female C57BL/6J mice were subjected to femoral shaft fracture and external fixation, and received daily treatment for three days with either phentolamine, propranolol, or butoxamine. They were analyzed early (at day 1) and late at day 21 post-fracture. Renal function was assessed via blood urea nitrogen measurement, while kidney injury was evaluated using histology and gene expression analysis. Results:While renal function remained within the physiological range, animals with fracture revealed signs of kidney damage one day after fracture, reflected by increased expression of kidney damage markers and oxidative stress indicators and histopathological changes. Cellular inflammation and proliferation were induced upon fracture but did not cause long-term fibrosis. By 21 days, these effects were no longer detectable, suggesting transient TRAKI. Adrenergic receptor (AR) blockade experiments clearly indicated a sympathetic contribution to this temporal renal response. α-AR-mediated effects in particular modulated the kidneys' response to oxidative stress, as phentolamine treatment reduced early oxidative stress markers. Furthermore, immune activation was only detected upon propranolol application. However, none of the treatments provided a sustained protective effect. Rather, a mixed outcome was observed in different aspects of TRAKI. Conclusion:Taken together, femoral fractures in mice can induce transient mild kidney injury, local cellular damage, and inflammation, while maintaining renal function. Adrenergic signalling appears to contribute to TRAKI development, which warrants further mechanistic investigation.
Aims:Accurate differentiation between periprosthetic joint infection (PJI) and aseptic osteolysis (AO) remains a major clinical challenge in revision joint arthroplasty. We examined bone biopsies for alterations in bone matrix integrity and the osteocyte lacunocanalicular network in order to differentiate between these pathologies. Methods:Bone biopsies were taken from areas of osteolysis in patients who underwent revision arthroplasty for either PJI, diagnosed according to 2018 International Consensus Meeting criteria, or AO. Controls were obtained during primary arthroplasty. Biopsies were assessed histologically by Masson's trichrome, silver and RGB trichrome staining, and for osteocyte lacunocanalicular characteristics. The diagnostic potential of histological measures was investigated using univariate area under the receiver operating characteristic curve (AUROC) analysis. Results:RGB trichrome staining was most effective for revealing both bone matrix and lacunocanalicular features. Osteocyte lacunar area and circularity were increased in PJI relative to both AO and Control bone. PJI bone exhibited reduced canalicular density compared to AO (p < 0.001), and shorter, narrower canaliculi than AO and Controls. Predictive univariate modelling revealed that all histological parameters measured except lacunar area were potentially diagnostic for PJI. Degraded bone matrix differentially predicted PJI (AUROC = 0.875, 88% sensitivity, 80% specificity) and AO (AUROC = 0.733, 63% sensitivity, 76% specificity), as did lacunar circularity (PJI: AUROC = 0.903, 75% sensitivity, 96% specificity; AO: AUROC = 0.797, 69% sensitivity, 84% specificity). Canalicular area fraction, length, and width all predicted PJI (AUROCs = 0.915, 0.982, 0.883), with canalicular length yielding 94% sensitivity and 100% specificity. Canalicular density differentially predicted PJI (AUROC = 0.770, 69% sensitivity, 80% specificity) and AO (AUROC = 0.757, 88% sensitivity, 60% specificity). Conclusion:Histological assessment of bone matrix degradation and the osteocyte lacunocanalicular network reveals new potential diagnostic markers for PJI to support clinical decision-making and provides novel measures for distinguishing PJI from AO, which may be particularly useful in cases of low-grade and chronic infections. Based on these findings, larger confirmatory studies are warranted.
Aims Although intra-articular vancomycin has demonstrated satisfactory outcomes for periprosthetic joint infection (PJI), dose and dosing frequency remain largely empirical. This study aimed to develop a target-based population pharmacokinetics (PK) model to predict local vancomycin exposure, and to evaluate the efficacy and safety of various regimens in patients with PJI. Methods Patients with PJI who received intravenous (IV) infusion or intra-articular injection of vancomycin were included. Population PK analysis was performed using nonlinear mixed effects modelling. Monte Carlo simulations were used to assess pharmacodynamic target attainment against Staphylococcus species, and to evaluate vancomycin-associated safety risks. Results A total of 450 plasma and synovial fluid samples from 161 patients with PJI were analyzed. The pharmacokinetics of vancomycin in synovial fluid were best described by a two-compartment joint model linked to a central plasma compartment. Creatinine clearancesignificantly affected systemic clearance, while age influenced the penetration from synovial fluid to the central compartment. Simulations suggested that intra-articular dosing of 500 mg once daily was sufficient for targets against Staphylococcus aureus and Staphylococcus epidermidis , whereas other coagulase-negative staphylococci required more intensive regimens, including 250 or 500 mg every 12 hours or 1,000 mg once daily. For patients with severe renal impairment, intra-articular administration alone provided adequate systemic exposure, and concomitant IV administration was not recommended. Conclusion The intra-articular population PK model accurately characterized vancomycin concentrations in plasma and synovial fluid, supporting optimized intra-articular dosing regimens in patients with PJI according to renal function and age. Cite this article: Bone Joint Res 2026;15(8):951–960.
Aims:To clarify the immunomodulatory mechanisms by which tibial cortex transverse transport (TTT) accelerates wound healing in a type 2 diabetic rat model, with particular focus on the dynamics of subsets of monocytes and macrophages. Methods:A total of 186 male Sprague-Dawley rats were induced as diabetic via a high-fat diet and streptozotocin. A full-thickness skin defect was created on the dorsum of the foot immediately following standard TTT surgery. Wound closure was monitored photographically. At defined timepoints (days 3 to 21), wound tissues underwent histological and immunofluorescence staining (haematoxylin and eosin, Masson's trichrome, picrosirius red, CD68/iNOS/mannose) to assess re-epithelialization, collagen organization, and M1/M2 macrophage populations. Flow cytometry of bone marrow and peripheral blood (CD43 and CD172a markers) quantified classical and non-classical monocyte subsets. Monocyte/macrophage involvement was probed by depleting these cells with clodronate liposomes versus phosphate-buffered saline liposomes. Results:TTT-treated rats achieved complete wound closure by day 21, markedly faster than fixator or sham controls. Histology revealed enhanced re-epithelialization, a thicker epidermis, well-organized type III collagen, and normalized collagen fibre directionality. Immunofluorescence demonstrated a rapid decline in proinflammatory M1 and an increase in reparative M2 macrophages from day 5 onward. Flow cytometry showed a pronounced surge of non-classical monocytes in bone marrow on day 3, followed by elevated circulating levels on days 3 to 6. Monocyte/macrophage depletion markedly delayed healing and disrupted collagen deposition. Conclusion:TTT is associated with accelerated diabetic wound repair, accompanied by preferential mobilization of non-classical monocytes and increased M2 macrophage polarization at the wound site. These findings are consistent with a mechanically induced immunomodulatory process that may contribute to improved healing outcomes.
Aims Fibroadipogenic progenitors (FAPs) are a group of resident muscle stem cells capable of differentiating into fibroblasts and adipocytes, contributing to intramuscular fibrotic and fatty degeneration after injury. However, FAPs are also thought to play a crucial role in muscle regeneration by facilitating satellite cell myogenesis. Despite this dual role, the precise functions of FAPs in muscle degeneration and regeneration remain unclear. This study aimed to utilize a FAP depletion mouse model to define the role of FAPs in two distinct, clinically relevant injury models of rotator cuff tears (RCTs) and tibialis anterior (TA) volumetric muscle loss (VML). Methods Six PDGFRα-Cre ERT /DTA mice were applied for fluorescence-activated cell sorting (FACS) evaluation of FAP depletion efficiency with tamoxifen induction. Then, two groups of ten PDGFRα-Cre ERT /DTA mice and five DTA mice underwent either unilateral supraspinatus and infraspinatus tendons and suprascapular nerve transection (RCT model) or the creation of a 4 mm diameter defect in the unilateral TA (VML model). To induce FAP depletion, tamoxifen or corn oil (control) was administered daily for two weeks before surgery. Gait analysis was conducted at six weeks post-surgery to evaluate shoulder or hindlimb function. Supraspinatus or TA muscles were harvested to assess muscle atrophy and for histological analysis. Results FACS analysis confirmed a 50% reduction in FAPs following tamoxifen administration in PDGFRα-Cre ERT /DTA mice. In the RCT model, FAP depletion significantly attenuated muscle atrophy and improved fibrosis, fatty infiltration (FI), and global shoulder function. Conversely, in the VML model, FAP depletion significantly decreased muscle fibrosis but had no effect on FI and functional outcomes. Conclusion Our results suggest that FAPs play distinct roles in muscle regeneration depending on the specific clinical context. These models can be used to further understand the different injury mechanisms and muscle-specific properties influencing FAP roles in musculoskeletal pathology. Cite this article: Bone Joint Res 2026;15(8):927–936.
Aims This study aimed to evaluate the differences in postoperative internal fixation system failure between two distinct pedicle screw designs, and to examine how variations in the transitional segment and thread distribution of these screws influence the bending mechanical properties of the rod-screw system. Methods A retrospective analysis was performed on 81 cases of thoracolumbar posterior internal fixation surgery from January 2020 to December 2023, focusing on comparing the postoperative fracture and loosening rates associated with the two pedicle screw designs. Finite element analysis was employed to assess the impact of different transitional segment and thread distribution designs of pedicle screws on stress distribution within the rod-screw system under physiological stress conditions in a T10-L2 fracture model. Dynamic and static bending performance tests were conducted on pedicle screws and rod-screw systems featuring various transition segment and thread distribution designs. Results The clinical analysis revealed significant variations in postoperative fracture rates among rod-screw systems with different pedicle screw designs (p < 0.05), while the rates of loosening remained largely consistent postoperatively. Finite element analysis and mechanical testing demonstrated that extending the transitional segment can mitigate the maximum stress across the entire rod-screw system and enhance the uniformity of stress distribution. This modification improves the bending performance of the pedicle screw and its rod-screw system, shifting the failure point from the pedicle screw to the connecting rod. Conversely, variations in thread distribution design exhibited minimal impact on the stress distribution and bending performance of the entire rod-screw system. Conclusion Pedicle screws with optimally extended transitional segments can effectively alleviate local stress concentrations and enhance the bending performance of the screw and its rod-screw system, thereby reducing the risk of postoperative screw fracture. Cite this article: Bone Joint Res 2026;15(4):383–396.
Aims Recombinant human (rh) insulin-like growth factor-1 (IGF1) treatment has been shown to restore growth velocity and height in children harbouring pregnancy-associated plasma protein-A2 ( PAPP-A2 ) mutations. The present study aimed to evaluate whether pharmacological modulation of the growth hormone (GH)/IGF1 system elicits sex-specific improvements in bone growth in a pappalysin 2 (Pappa2)- deficient mouse model of growth impairment, and to identify the associated signalling pathways. Methods Pappa2 knockout ( Pappa2 ko/ko ) mice of both sexes received daily treatment with rhGH, rhIGF1, or rhPAPP-A2 from postnatal day (PND) 5 to PND 35. The IGF1 system, bone remodelling factors, cannabinoid receptors, and intracellular signalling were analyzed in bone. Results At the onset of puberty, hormone-treated knockout Pappa2 ( Pappa2 ko/ko ) mice exhibited increased body length and weight, along with a higher femur weight-to-length ratio following rhGH or rhPAPP-A2 administration. In Pappa2 ko/ko females, hormone treatments reduced the bone resorption marker osteopontin, particularly following rhPAPP-A2, which also led to decreased expression of cannabinoid receptors ( CNR1 , CNR2 , and GPR55 ). Compared to rhGH, both rhPAPP-A2 and rhIGF1 specifically decreased the IGF binding protein Igfbp5 and increased expression of the bone formation markers osteocalcin and collagen I in females. These effects were accompanied by elevated levels of phosphorylated signal transducer and activator of transcription 3 (STAT3). Pappa2 deficiency and hormone therapy were associated with numerous sex-specific differences in bone IGF1 binding, bone remodelling, cannabinoid receptors, and signal transducer and activator of transcription 3 (STAT3) signalling. Conclusion These findings support rhPAPP-A2 as a promising therapeutic candidate for mitigating postnatal bone growth retardation by increasing bone formation and reducing resorption through cannabinoid receptor modulation in a female-specific manner. Cite this article: Bone Joint Res 2026;15(5):519–536.
Aims Musculoskeletal (MSK) diseases involve complex immune mechanisms. Conventional flow cytometry is restricted by spectral overlap, limiting multidimensional immune characterization. Mass cytometry by time-of-flight (CyTOF) can measure over 40 proteins per cell using metal-tagged antibodies and time-of-flight detection, providing deep immune phenotyping. The aim of this narrative review was to summarize the applications of CyTOF in the study of human orthopaedic and rheumatic diseases, highlight key immune findings including shared markers, and identify gaps to guide future research and panel standardization. Methods A literature search of peer-reviewed studies published from 1 January 2014 to 31 December 2024 was conducted using PubMed, Scopus, and Web of Science. Search terms included “CyTOF” and “mass cytometry”. Studies were included if CyTOF was applied to human MSK disorders with immune or inflammatory components and if the full text was available in English. Data extracted included disease type, sample source, computational pipeline, immune cell types analyzed, and main findings. Results A total of 22 studies were included. Since some studies reported results for more than one disease, the total number of disease-specific entries was 26: rheumatoid arthritis (n = 13), osteoarthritis (n = 4), psoriatic arthritis (n = 3), juvenile idiopathic arthritis (n = 2), ankylosing spondylitis (n = 1), idiopathic inflammatory myopathies (n = 1), and post-surgical immune monitoring (n = 2). Human models were represented. CyTOF identified disease-specific immune cell subsets, cytokine profiles, and treatment-response signatures. No eligible studies addressed osteoporosis or osteonecrosis likely reflecting that these conditions would yield low immune-cell density and/or technical challenges in acquiring bone tissue. Eight recurrent markers emerged across diseases: program cell death protein 1 (PD-1), inducible T-cell costimulator (ICOS), CXC motif chemokine receptor (CXCR)5, CXCR4, phosphorylated signal transducer and activator of transcription 4 protein (pSTAT3), tumour necrosis factor receptor II (TNFRII), p16 inhibitor of cyclin-dependent kinase 4a (p16INK4a), and cluster of differentiation (CD)180, which reflect shared pathways of inflammation, senescence, and tissue damage. Conclusion CyTOF enables high-dimensional immune profiling in MSK diseases, offering insights into pathogenesis, treatment response, and patient stratification. Broader application of this technology to underexplored conditions is warranted. A minimal eight-marker backbone may enhance panel harmonization and support future multicentre translational studies in orthopaedic immunology. Cite this article: Bone Joint Res 2026;15(5):497–507.
Orthopaedic implants consist of engineered devices for various surgical uses, such as plates or nails used to fix fractures; plates, rods, or cages used for spinal fusion, total hip or knee arthroplasties, and osteoconductive bone scaffolds. The implant design process typically involves the complicated interaction of interdisciplinary teams, client consultation, concept generation, concept ranking, prototype fabrication, engineering analysis, etc. However, the process can also be described as having four major aspects, each of which has a feedback loop if modifications are needed. The first is the design and fabrication, which can include factors such as geometry, surface finish, special features, material selection, and methods of fabrication. The second involves mechanical/engineering analysis, which could involve factors such as stress risers, stress shielding, elastic stiffness, failure strength, and fatigue life. The third is biological/clinical analysis, which may involve factors such as biocompatibility, bioresorbability, bone remodelling, surgical simplicity, and clinical outcomes. The fourth is marketplace evaluation, which might involve factors such as cost-effectiveness, patent acquisition, regulatory approval, demographic suitability, and ecological sustainability. These aspects, or the specific factors within each aspect, can occur sequentially step by step, simultaneously side by side, in different orders, or by some combination of all of these options. This article is a brief practical introduction to the design process for orthopaedic implants. Cite this article: Bone Joint Res 2026;15(5):577–582.
